The JAK2 V617F Allele Burden in Latent Myeloproliferative Neoplasms Presenting with Splanchnic Vein Thrombosis.

Abstract

To the Editor: Myeloproliferative neoplasms (MPN) are a recognised underlying cause of splanchnic vein thrombosis (SVT) and by strict definition, have abnormal peripheral full blood counts (FBC) and morphological features [1, 2]. The most commonly observed acquired mutation in MPN is the JAK2 V617F, detected in the majority of polycythemia vera patients and 50–60 % of patients with essential thrombocythemia and primary myelofibrosis. Assessment of the JAK2 V617F allele burden by quantitative PCR (qPCR) in MPN has been shown to be of value in measuring response to certain therapies [3], and can be predictive of thrombotic risk and myelofibrotic or leukemic transformation. A significant proportion of patients with otherwise unexplained SVT are found to have evidence of the JAK2 V617F mutation in the presence of a normal FBC: a latent MPN [4]. Despite this well documented phenomenon, data on the impact of the JAK2 V617F and its allele burden on subsequent disease evolution in those patients with a latent MPN are scarce [5–7]. In order to investigate this issue, the incidence of JAK2 V617F-positive patients presenting with an SVT from a single-centre was identified, the JAK2 V617F allele burden of those patients with both a latent and overt MPN were determined at this time, with subsequent follow up of FBC indices. Of 171 JAK2 V617F-positive patients identified in a single-centre between March 2006 and October 2013, 17 (10 %) had a history of SVT comprising portal vein thrombosis (n = 3), hepatic vein thrombosis (n = 6), splenic vein thrombosis (n = 1), combined portal and superior mesenteric vein thrombosis (n = 3), combined portal and splenic vein thrombosis (n = 2), and combined portal superior mesenteric and splenic vein thrombosis (n = 2). The median age of SVT presentation was 37 years (range 14–61 years) and of which ten patients were male and seven were female. One patient had known essential thrombocythaemia and of the remaining 16, seven (44 %) had a normal and nine (56 %) an abnormal FBC (thrombocytosis: n = 5; leukocytosis: n = 2; polycythemia: n = 1; cytopenias: n = 1). The JAK2 V617F allele burden was retrospectively assessed by qPCR [8] in archival peripheral blood DNA from the time of SVT. No statistically significant difference was observed in the JAK2 V617F allele burden between those patients with a latent MPN (median 9.6 %, range 6.8–55.5 %) and those with an overt MPN (median 19.8 %, range 3.1–62.1 %) (P = 0.475). Intriguingly, and despite the further finding of a morphologically evident MPN on bone marrow biopsy in two of these patients, all seven JAK2 V617F-positive patients with an SVT who had a normal FBC continue to do so at a median follow-up of 54 months (range 34–90), with none receiving any cytoreductive therapy. The JAK2 V617F mutation provides a diagnostic marker of clonal disease, in the majority of patients with classical MPN with determination of the mutant allele burden kinetics by qPCR able to provide information on disease progression and risk of thrombosis. However, there remains considerable uncertainty regarding the prognostic significance of the JAK2 V617F * Stephen E. Langabeer slangabeer@stjames.ie